The Journal of Clinical Pharmacology最新文献

{"title":"Lack of Modulation of In Vivo Activity of Organic Anion Transporters 1 and 3 in Pregnancy Using Furosemide as a Probe","authors":"Júlia Werner Vieira BSc,&nbsp;Patrícia Pereira dos Santos Melli MD,&nbsp;Geraldo Duarte PhD, MD,&nbsp;Vera Lucia Lanchote PhD,&nbsp;Jhohann Richard de Lima de Benzi PhD","doi":"10.1002/jcph.70167","DOIUrl":"10.1002/jcph.70167","url":null,"abstract":"<p>Pregnancy induces physiological changes that can alter drug disposition, yet little is known about their impact on renal transporters such as organic anion transporters 1 and 3 (OAT1/3). This study aimed to evaluate the in vivo activity of OAT1/3 during pregnancy using furosemide as a probe substrate. Twelve healthy non-pregnant women and 10 healthy pregnant women, mostly in the third trimester, received a single 40-mg oral dose of furosemide under fasting conditions. Serial blood and urine samples were collected for up to 24 h. Pharmacokinetic parameters were estimated by non-compartmental analysis, including time to maximum plasma concentration (t_max), maximum plasma concentration (C_max), area under the plasma concentration–time curve (AUC), amount excreted in urine (Ae), fraction excreted unchanged in urine (f_e), unbound plasma fraction (<i>fu</i>), apparent clearance (CL/F), renal clearance (CL_R), non-renal clearance (CL_NR), secretory clearance (CL_SEC), and metabolic clearance via furosemide glucuronide formation (CL_M). Compared with non-pregnant women, pregnant women exhibited significantly lower exposure, C_max, Ae, and f_e values, while CL/F and CL_NR were significantly increased. In contrast, no significant differences were observed for CL_R and CL_SEC, indicating preserved OAT1/3 activity. These findings suggest unchanged OAT1/3-mediated renal secretory activity during pregnancy contrast with the published literature for other OAT1/3 substrates, which have, in most cases, reported an increase in OAT1/3 activity during pregnancy. Instead, the data raise the hypothesis that changes in intestinal absorption of furosemide, possibly influenced by gestational regulation of intestinal transporters, may contribute to the lower exposure.</p>","PeriodicalId":22751,"journal":{"name":"The Journal of Clinical Pharmacology","volume":"66 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12927693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147272392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Concentration-QTc Analysis as an Alternative to TQT Studies: Findings From QT Evaluation and Safety Labeling Decisions in Japan","authors":"Tsubasa Wakabayashi MSc,&nbsp;Mamoru Narukawa Ph.D","doi":"10.1002/jcph.70169","DOIUrl":"10.1002/jcph.70169","url":null,"abstract":"<p>Thorough QT (TQT) studies have long been the regulatory gold standard for evaluating QT prolongation risk. With the implementation of the ICH E14 Q&amp;A updates, various alternatives to TQT studies, referred to as QT pathways, have gained attention. However, it remains unclear whether concentration-QTc (C-QTc) analysis or other QT pathways carry the same regulatory weight as TQT studies, particularly when making safety labeling decisions. To address this issue, we investigated the relationship between QT evaluation methods and QT prolongation–related safety labeling for 295 new active substances approved in Japan between 2015 and 2024. These substances were grouped based on their respective QT pathways, and the consistency between QT assessment results and the corresponding labeling outcomes was evaluated. C-QTc analyses showed strong concordance in labeling outcomes and Phase 3 QT evaluation results, supporting their regulatory acceptability comparable to that of TQT studies. In contrast, the Q&amp;A 6.1 pathway, primarily used for oncology drugs and substances with poor tolerability, exhibited more frequent inconsistencies between clinical pharmacology QT evaluation results and safety labeling. There was a noticeable tendency to rely more heavily on Phase 3 QT evaluation results to support labeling decisions. These findings suggest that C-QTc analysis could be more broadly adopted in future regulatory submissions in Japan and highlight the importance of early strategic planning, including decisions on ECG monitoring and early dialogue with regulators, when utilizing the Q&amp;A 6.1 pathway.</p>","PeriodicalId":22751,"journal":{"name":"The Journal of Clinical Pharmacology","volume":"66 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146221488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism-Based Predictions of Local Tissue and Systemic Exposure for Drug Products Delivered Through the Female Reproductive Tract","authors":"Xinnong Li MS,&nbsp;Thomas Straubinger MS,&nbsp;Lisa C. Rohan PhD,&nbsp;Sharon L. Achilles MD, PhD,&nbsp;Beatrice A. Chen MD, MPH,&nbsp;Guru Valicherla PhD,&nbsp;Zhongfang Zhang PhD,&nbsp;Mark Donnelly PhD,&nbsp;Eleftheria Tsakalozou PhD,&nbsp;Liang Zhao PhD,&nbsp;Robert Bies PharmD, PhD","doi":"10.1002/jcph.70159","DOIUrl":"10.1002/jcph.70159","url":null,"abstract":"<p>Effective drug delivery through the female reproductive tract (FRT) presents unique challenges due to the lack of robust predictive models for drug exposure via this route. Addressing this gap, we developed and evaluated a comprehensive whole-body physiologically based pharmacokinetic (PBPK) model that incorporates anatomical and physiological information of the FRT. This model was calibrated using both published and experimental data for the drug levonorgestrel (LNG), administered via oral, vaginal, and intrauterine routes. The PBPK model simulates drug absorption, distribution, and elimination, providing predictions of local tissue concentrations and systemic exposure. The majority of observations can be contained within or overlaid with the simulated profiles. Noteworthy is the model's capability to predict the pharmacokinetics of LNG with reasonable precision across different administration routes, thereby demonstrating its potential utility in supporting drug development and regulatory decisions. The application of this model allows for exploration of drug formulations and dosing regimens, reducing the reliance on extensive clinical trials. Furthermore, the model may potentially be used to facilitate generic drug development, and thus promote generic competition, for drug products that are important in women's health. By bridging critical knowledge gaps, this model facilitates in silico evaluation of drugs administered through the FRT, potentially fostering advancements in therapeutic strategies and patient care.</p>","PeriodicalId":22751,"journal":{"name":"The Journal of Clinical Pharmacology","volume":"66 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12910638/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146214657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics, Disposition, and Biotransformation of Laroprovstat in Humans: In Vivo and In Vitro Evaluations","authors":"Xue-Qing Li PhD,&nbsp;Marie Elebring PhD,&nbsp;Maria Heijer MSc,&nbsp;Rick Vega PhD,&nbsp;Anna Rudvik BSc,&nbsp;Nand Singh MD,&nbsp;Rebecca Simmonds ,&nbsp;Marta Pelay-Gimeno PhD,&nbsp;Jelle Reinen PhD,&nbsp;Charlotta Vedin-Nilsson BSc,&nbsp;Isabella Bonner Karlsson PhD,&nbsp;Lloyd Tanner PhD,&nbsp;Vijender Panduga PhD,&nbsp;Catarina Nilsson PhD,&nbsp;Jaya Rosenmeier MD,&nbsp;April M. Barbour PhD","doi":"10.1002/jcph.70162","DOIUrl":"10.1002/jcph.70162","url":null,"abstract":"<p>Laroprovstat (AZD0780) is a small-molecule, oral PCSK9 inhibitor being developed for hypercholesterolemia. In vitro experiments and a two-part clinical study were conducted to characterize laroprovstat routes of elimination, metabolism, and absolute oral bioavailability. Laroprovstat was incubated in human hepatic spheroids from two different donors with and without ketoconazole to examine metabolite formation. A clinical study was conducted in eight healthy male participants, whereby in Part 1 each subject received a single oral dose of 60 mg as tablets of laroprovstat with a 100-µg IV infusion of [¹⁴C]laroprovstat solution to determine absolute oral bioavailability. In Part 2, a single oral dose of 60-mg [¹⁴C]laroprovstat solution was administered for disposition and biotransformation characterization. Based on in vitro studies, CYP3A are the predominant enzymes involved in the oxidative metabolism of laroprovstat, accounting for approximately 90% of laroprovstat metabolism. From the clinical study, laroprovstat is highly orally bioavailable, 78.4%. Laroprovstat was extensively metabolized with most of the dose excreted as oxidative metabolites with some additional conjugation. Only 15% and 6% of the dose was eliminated as parent in the urine and feces, respectively. No major circulating metabolites were identified that require further safety assessment or in vitro evaluation of DDI potential, aligned with the analysis of metabolites in plasma after repeated administration of laroprovstat from the MAD study. Renal elimination of total radioactivity was 64%, compared to 26% in the feces. Laroprovstat does not undergo significant chiral interconversion. Laroprovstat was well tolerated with no new safety concerns. These studies successfully characterized the ADME properties of laroprovstat.</p>","PeriodicalId":22751,"journal":{"name":"The Journal of Clinical Pharmacology","volume":"66 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146202978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of Pediatric Dosing for Mepolizumab in Severe Asthma Based on Extrapolation of Data From Adult Patients and a Phase II Open-Label Pediatric Trial","authors":"Atul Gupta MD(Res),&nbsp;Isabelle J. Pouliquen PharmD,&nbsp;Wanda Phipatanakul MD, MS,&nbsp;Daren Austin PhD,&nbsp;Glenn Whelan PharmD,&nbsp;Robert G. Price MSc,&nbsp;Tricia Finney-Hayward PhD,&nbsp;Sabine Derey PharmD,&nbsp;Jonathan Steinfeld MD","doi":"10.1002/jcph.70155","DOIUrl":"10.1002/jcph.70155","url":null,"abstract":"<p>The benefit–risk profile of mepolizumab in severe asthma was established through clinical trials in adults, leading to EU and US approvals in 2015. To support a pediatric indication (≥6 years), an extrapolation approach was implemented. This extrapolation and its validation were informed by data from Phase III trials in adults (N = 1841) and adolescents aged 12-17 years (N = 37) with severe asthma, an open-label trial in children aged 6-11 years (N = 36), and a trial in children aged 2-11 years (N = 32) and adolescents aged 12-17 years (N = 27) with eosinophilic esophagitis. Population pharmacokinetic and pharmacokinetic/pharmacodynamic meta-analyses demonstrated consistent mepolizumab pharmacokinetic and blood eosinophil reduction across age groups and diseases, with bodyweight the only covariate of exposure and absolute bioavailability also a covariate in children aged 6-11 years. Baseline blood eosinophil count and disease type were the only covariates of response. In severe asthma, mepolizumab reduced the annualized rate of clinically significant exacerbations by 40% in adolescents and 54% in adults versus placebo. Bootstrap resampling and Bayesian analyses supported similar efficacy between adolescents and adults, and responses in children aged 6-11 years were consistent with older groups. Safety evaluations revealed no unique safety concerns in pediatric patients with severe asthma. This extrapolation strategy, implemented as an innovative approach to pediatric clinical development of mepolizumab in severe asthma, was validated and provided the scientific basis for dosing recommendations and for EU regulatory approval in patients aged ≥6 years in 2018.</p>","PeriodicalId":22751,"journal":{"name":"The Journal of Clinical Pharmacology","volume":"66 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12907775/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146202830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Explaining clinically important variability in response to simvastatin treatment using a PBPK/PD approach","authors":"Wonho Kang PhD,&nbsp;Ana Carolina Conchon Costa PhD,&nbsp;Jose Ivan Marques Medeiros PhD,&nbsp;Brian Cicali PhD,&nbsp;Wilson Salgado Junior MD, PhD,&nbsp;Stephan Schmidt PhD,&nbsp;Natalia Valadares de Moraes PhD","doi":"10.1002/jcph.70163","DOIUrl":"10.1002/jcph.70163","url":null,"abstract":"<p>Understanding exposure-response relationships is critical for the selection of an optimal drug dose that balances efficacy and safety. For simvastatin (SV), plasma concentrations may not accurately reflect target site exposure, because its pharmacologic effect is linked to intrahepatic unbound concentrations of its active form, simvastatin hydroxy acid (SVA). SVA is taken up into hepatocytes via the OATP1B1 transporter (encoded by <i>SLCO1B1</i>), where it is metabolized by CYP3A4. Physiological conditions such as obesity and post-Roux-en-Y gastric bypass (RYGB) surgery can alter drug disposition and enzyme activity, impacting hepatic drug exposure. This study aimed to evaluate gene–drug interaction and disease–drug interactions affecting SVA pharmacokinetics and optimize SV dosing by linking intrahepatic unbound SVA concentration to LDL-cholesterol (LDL-C) reduction using a physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) modeling approach. Simulations across doses, genotypes, and populations revealed that <i>SLCO1B1</i> c.521T&gt;C variation significantly affects plasma SVA exposure, but not hepatic SVA exposure. Obese individuals exhibited higher plasma and hepatic SVA exposure than non-obese individuals. A 20 mg dose achieved a 30–49% LDL-C reduction in obese subjects, regardless of <i>SLCO1B1</i> genotype, whereas non-obese subjects may require 40 mg to achieve similar efficacy. In conclusion, systemic drug concentration or genotyping alone are insufficient to predict statin response. Instead, information on genetic and physiological variability needs to be integrated into a PBPK/PD framework to select optimal doses across diverse populations.</p>","PeriodicalId":22751,"journal":{"name":"The Journal of Clinical Pharmacology","volume":"66 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146202835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physiologically Based Pharmacokinetic Modeling of Lurasidone, an Antipsychotic Drug: Impact of CYP3A4 Polymorphisms and Hepatic Impairment on Exposure and Dose Optimization","authors":"Seung-Hyun Jeong PhD,&nbsp;Yunha Noh PhD,&nbsp;Ji-Hun Jang PhD","doi":"10.1002/jcph.70164","DOIUrl":"10.1002/jcph.70164","url":null,"abstract":"<p>Lurasidone is an antipsychotic drug used to treat schizophrenia and bipolar depression, primarily metabolized by cytochrome P450 3A4 (CYP3A4). Its pharmacokinetics (PK) can vary depending on CYP3A4 genetic polymorphisms and liver function, often requiring clinical dose adjustments. However, there is a lack of systematic tools for quantitatively predicting such interindividual variability. This study aimed to develop a physiologically based pharmacokinetic (PBPK) model of lurasidone that incorporates CYP3A4 polymorphisms and hepatic impairment to support dose optimization across clinical populations. The PBPK model was constructed using published in vitro and clinical PK data. Model validation was performed by comparing simulations with independent clinical trials. We conducted single- and multiple-dose simulations reflecting CYP3A4 genotype (wild-type vs. *15 allele) and hepatic impairment (Child-Pugh A, B, C). Predicted exposures were compared with a reference population (CYP3A4 wild-type, normal liver, 80 mg/day) to explore dose adjustment needs. Simulation results demonstrated increased exposure with worsening liver function, and decreased exposure in the presence of the *15 allele due to enhanced metabolism. Based on these results, reduced doses (20-40 mg/day) were recommended for wild-type patients with hepatic impairment, while higher doses (up to 240 mg/day) were needed for *15 carriers with normal liver function. Adjusted doses resulted in stable therapeutic exposures across groups. This PBPK model offers a quantitative strategy for individualizing lurasidone dosing based on genotype and hepatic function. It provides a valuable precision dosing tool to ensure safety and efficacy in vulnerable patient populations.</p>","PeriodicalId":22751,"journal":{"name":"The Journal of Clinical Pharmacology","volume":"66 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146202973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deconvoluting Gut Versus Liver Cytochrome P450 3A4 Function: Drug Probes, Biomarkers, and Tissue Biopsy","authors":"David Rodrigues PhD","doi":"10.1002/jcph.70165","DOIUrl":"10.1002/jcph.70165","url":null,"abstract":"<p>Cytochrome P450 3A4 (CYP3A4) is an important drug-metabolizing enzyme, whose function is impacted by age, sex, body weight, pregnancy, and disease. It is also the site of major drug interactions involving inhibition and induction. Because CYP3A4 is expressed in the intestine and liver, investigators have sought to study its function in both organs. As reviewed in the current narrative, approaches have included the profiling of tissue biopsy samples, use of novel plasma-based liquid biopsies, studies with individuals undergoing liver transplant, intravenous (IV) probe pharmacokinetics (PK) to measure hepatic CYP3A4 activity (e.g., midazolam and erythromycin breath test, ERBT), oral probe PK to differentially capture gut and liver CYP3A4 activity (e.g., midazolam and alprazolam), biomarkers (e.g., 6β-hydroxy cortisol/cortisol [6βHC/C] and 1β-hydroxy deoxycholic acid/deoxycholic acid [1βHDCA/DCA] urine ratio, and 4β-hydroxy cholesterol/cholesterol [4βHC/C] plasma ratio), modeling (e.g., static and physiologically based PK), and dosing of agents to inhibit intestinal CYP3A4 (e.g., grapefruit juice [GFJ]). Overall, there is also broad consensus that IV midazolam PK and ERBT are reflective of liver CYP3A4, that oral midazolam reports both gut and liver CYP3A4, and that one can selectively inhibit gut CYP3A4 using GFJ. Data for biomarkers are mixed, however, indicating that 4βHC/C plasma ratio is largely reflective of liver CYP3A4 in the basal state, unlike 6βHC/C and possibly 1βHDCA/DCA urine ratio. Literature reports also showcase challenges when correlating different CYP3A4 trait measures across subjects, impacted by genotype (e.g., <i>CYP3A5</i>, P-glycoprotein), sex, body weight, and the contribution of gut (versus liver) to probe drug and biomarker disposition.</p>","PeriodicalId":22751,"journal":{"name":"The Journal of Clinical Pharmacology","volume":"66 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12905028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146195881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Model-Informed Abatacept Dose Recommendation in Pediatric Patients With Acute Graft Versus Host Disease","authors":"Rui Zhong PhD,&nbsp;Kelly Maxwell PhD,&nbsp;Julie Passarell MA,&nbsp;Bindu Murthy PharmD,&nbsp;Urvi Aras PhD,&nbsp;Daphne Williams PhD, PharmD","doi":"10.1002/jcph.70156","DOIUrl":"10.1002/jcph.70156","url":null,"abstract":"<p>This study uses a population pharmacokinetic (PPK) approach to provide abatacept dosing recommendations in pediatric patients 2 to &lt; 6 years of age receiving unrelated donor hematopoietic stem cell transplantation (HSCT) due to hematologic malignancies (HMs), for the prophylaxis of acute graft-versus-host disease (aGVHD). An intermediate PPK model was developed and refined to include data from 904 patients aged 2–17 years with juvenile idiopathic arthritis administered with subcutaneous abatacept. Then, PK simulations were performed using the final PPK model for virtual pediatric patients aged 2 to &lt; 6 years administered with either intravenous abatacept, fixed abatacept doses, or loading doses followed by maintenance dosing. The final model characterized abatacept exposure well using a linear, two-compartment model including absorption parameters (KA and F1), and generated parameter estimates comparable to previously published models. Further simulations of abatacept exposure in 10,000 virtual patients aged 2 to &lt;6 years revealed that a 15-mg/kg loading dose followed by 12-mg/kg maintenance doses achieved exposure levels similar to adults at risk of aGVHD, and therefore was selected for these patients. Additionally, an exposure–response (E-R) safety analysis in patients aged ≥6 years with HMs undergoing HSCT showed no significant relationship between abatacept exposure and occurrence of infection, confirming the safety of abatacept in these patients. The recommended dosing regimen for pediatric patients aged 2 to &lt;6 years at risk of aGVHD is a 15-mg/kg loading dose on Day −1, followed by 12 mg/kg for the remaining doses on Days 5, 14, and 28.</p>","PeriodicalId":22751,"journal":{"name":"The Journal of Clinical Pharmacology","volume":"66 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12902727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146182848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug Administration via Enteral Feeding Tubes: A Landscape Analysis of Information in Drug Product Labeling","authors":"Sherbet Samuels PhD,&nbsp;Daniel Denisenko PharmD,&nbsp;Susan Abdel-Rahman PharmD,&nbsp;Elimika Pfuma Fletcher PharmD, PhD, FCP","doi":"10.1002/jcph.70160","DOIUrl":"10.1002/jcph.70160","url":null,"abstract":"<p>Oral drug products are sometimes administered via enteral feeding tubes in populations with temporary or long-term swallowing disorders or difficulties. Health care providers require product-specific information regarding appropriate administration of drug products through enteral tubes to avoid occlusion of tubes and ensure the safe and effective use of the drug products. In this review, the enteral tube-related information in drug product labeling is characterized to better understand how such information is conveyed to health care professionals to help inform their clinical decision-making. The review identified 71 unique drug products with labeling related to administration via enteral feeding tube. Of those, 85% discussed the type of feeding tube and 46% discussed enteral tube size. Only 14% discussed the tubing material and 8% discussed timing of enteral feeds as it relates to dosing. The effect of enteral tube administration on the pharmacokinetics of the drug was only included in 18% of the drug product labeling. The high variability in the type and extent of enteral tube-related information in the drug product labeling suggests that innovative strategies are needed to help inform optimal use of drug products administered using this method. The few labeling that discuss feeding tube administration raises broader questions of if, and how, these data should be more consistently studied and included in labeling. Collaborative efforts from multiple stakeholders including drug developers and regulators can effectuate improvements in this area.</p>","PeriodicalId":22751,"journal":{"name":"The Journal of Clinical Pharmacology","volume":"66 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146151081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}